O. formigenes colonization may be inhibited by antibiotics

Winston-Salem, NC-Many commonly prescribed antibiotics may inhibit colonization of Oxalobacter formigenes, a bacterium that lowers the risk of calcium oxalate calculi, according to results from a recent study.

Strategies for stone prevention traditionally involve manipulation of the urinary milieu by either dietary or medical means. Recently, the involvement of bacterial colonization in assessment of stone risk has been considered. Specifically, colonization with O. formigenes has been shown to decrease the risk of forming calcium oxalate stones. O. formigenes is a gram-negative anaerobic bacterium that is present in the gastrointestinal tract and serves to metabolize ingested oxalate. It has been proposed that the absence of O. formigenes could increase the risk of calcium oxalate calculi.

Given that antibiotics are widely used for a variety of common disorders, researchers from Wake Forest University, Winston-Salem, NC evaluated the sensitivity of O. formigenes to several commonly used antibiotics. The research, presented by co-author Patrick Mufarrij, MD, at the 2010 World Congress on Endourology and SWL in Chicago, examined the in vitro minimal inhibitory concentration (MIC) of 15 commonly prescribed antibiotics. MIC was assessed using a two-fold serial broth dilution method and confirmed with an ion chromatography spectrophotometer.

"A significant number of antibiotics may impact colonization with O. formigenes," the authors concluded.

Given that calcium oxalate stones account for 90% of all calculi, the implications of this research are immediately evident. The authors note that 13% of all males and 7% of all females have at least one stone event in their lifetime. O. formigenes is critical to both gastrointestinal and renal health by metabolizing the excess oxalate obtained by the diet, the authors add.

Typically, the human colon has a volume of 1.8 liters and excretes roughly 150 to 200 grams of stool per day. Colonized stool usually contains between 107 and 108 colony-forming units of O. formigenes per gram of stool. Dr. Mufarrij explains that many antibiotics are excreted either unchanged or as an active metabolite in the stool. For example, about 15% to 40% of ciprofloxacin is excreted in the stool. This fraction of a 500-mg tablet far exceeds the MIC of ciprofloxacin, which means that this excreted amount will be present in more than adequate dosage to affect the enteric O. formigenes.

Results may guide antibiotic use

This information is potentially useful to clinicians for multiple reasons. Primary care physicians and urologists alike prescribe antibiotics for a variety of conditions. Patients with a history of stone disease may benefit from avoidance of the antibiotics identified by the researchers as effective against O. formigenes. For example, a patient with a history of stone disease could be treated for a urinary tract infection with trimethoprim/sulfamethoxazole, should the sensitivities allow use of this agent.

In addition, the use of calcium supplements in stone formers previously treated with effective agents to bind excess oxalate could be considered, although Dr. Mufarrij pointed out a caveat.

"Individual stool culture and sensitivity results would have to be assessed on a patient by patient basis," he said.

Still, the researchers admit that further re-search will be necessary to answer certain critical questions before the information will be clinically useful. For one, the process of re-colonization, including whether it happens and how long it takes, is poorly understood. Also, it has yet to be documented in vivo that the absence of O. formigenes results in clinically significant hyperoxaluria. Surely, future research will examine these issues.

Nonetheless, clinicians make innumerable decisions regarding antibiotic use, and these decisions are often arbitrary. This study will at the very least encourage a thoughtful decision-making process in patients at risk for nephrolithiasis.